Summary The objective of this proposal is to develop a back-irradiated (BI) active matrix flat-panel imager (AMFPI) with programmable avalanche gain. It will have wide dynamic range, high detective quantum efficiency (DQE) and high frame rate. The proposed detector employs three major components: a structured cesium iodide (CsI) scintillator with thickness up to twice that in existing AMFPI; an avalanche amorphous selenium (a-Se) photoconductor, HARP (High-gain Avalanche Rushing amorphous Photoconductor), to convert the optical photons from CsI to charge and provide a programmable gain; and a large area metal-oxide (MO) thin film transistor (TFT) array to read out the image electronically at 100 frames per second (fps). The proposed detector is called BI-SHARP-AMFPI (Back-Irradiated Scintillator- HARP Active Matrix Flat-Panel Imager). It is capable of producing x-ray quantum noise limited images at the lowest dose expected for x-ray imaging (0.1 ?R), which virtually has only one x-ray photon per pixel. For high dose applications (e.g. radiography) the gain of HARP will be decreased to ensure wide dynamic range without detector saturation. With BI, the majority of x-rays interact closer to the optical sensor, thereby permitting much thicker CsI to improve DQE at high kVp used in CBCT. The carrier mobility in MOTFT is more than an order of magnitude higher than a-Si TFT, permitting readout rate up to 100 fps, which is desired in CBCT. The objectives will be accomplished through the following three specific aims: (1) Optimize BI-SHARP-AMFPI detector configuration; (2) Develop the optimal HARP sensor structure for BI-SHARP-AMFPI; (3) Develop prototype BI-SHARP-AMFPI to prove feasibility and validate design considerations. Once these aims are accomplished a new AMFPI ready for clinical translation will be resulted, and permit major advancements in the most demanding x-ray imaging application: real-time imaging and CBCT for guidance of interventional procedures.